Monogalatosyldiacylglycerides (MGDG) may generally be obtained from a number of higher plant sources (including vegetables such as lettuce, broccoli, wheat, and alfalfa), from the central nervous system tissues of animals, and from a variety of macro- and micro-marine algae. However, monogalactosyldiacylglycerides containing the polyunsaturated fatty acid eicosapentaenoic acid (i.e., EPA) are only found in marine algae. More specifically, monogalactosyldiacylglycerides (i.e., MGDG) with the highest content of eicosapentaenoic acid are found in cold water marine micro-algae species. These eicosapentaenoic-acid containing glycerides (i.e., MGDG-EPA) are synthesized along with many other algal products (e.g., pigments, phospholipids, and other glyceryl lipids such as sulphoquinovosyldiacylglycerides, abbreviated SQDG, and diacylglyceryl-N,N,N-trimethylhomoserine, DGTS), thus making the reproducible isolation of useful quantities of high purity compositions complex and burdensome. Purity is particularly important for pharmaceutical and cosmetic compositions because chlorophylls and glycerolipids with similar solubilities may exhibit undesirable properties, e.g., potentiation of inflammation.
The therapeutic potential of EPA has fascinated medical scientists for more than two decades (1). There is continued interest in whether polyunsaturated fatty acids act as precursors of eicosanoid cascade-derived second messengers in inflammation or function via mechanisms independent of these messengers, e.g., by cytokine inhibition (2). Until recently, EPA used in studies of inflammation has been a free acid or sodium salt, a methyl or ethyl ester, or a component of fish oil or dietary fish, primarily in the form of triacylglycerols. Studies have generally employed EPA compounds delivered systemically, generally by ingestion, or have related to in vitro assays. Investigations with these EPA compounds have led to a `substrate substitution hypothesis` according to which EPA may take its effects by (i) transfer of EPA from applied lipids to cell membrane phospholipids (3); (ii) release of free EPA from putative membrane storage deposits through the action of phospholipases (4); and, (iii) substitution of EPA for arachidonic acid (AA) in metabolism with resultant production of less effective (or lower levels of) inflammatory mediators (5,6). At odds with this hypothesis is a preliminary report by Krueger et al. who found anti-inflammatory activity associated with an acylated-EPA, (in an amphiphilic lipid extracted from marine microalgae) and also an acylated-AA analogue of the algal lipid (7). The reported activity of the acylated-AA is difficult to accord with the substrate substitution hypothesis, since metabolism of acylated-AA would be expected to result in release of appropriate inflammatory mediators. However, the inflammation may be triggered through multiple different pathways, including at least bradykinin system proteins, complement and coagulation activation fragments, factors released from platelets such as platelet factor 4, and mediators of immediate type hypersensitivity, e.g., serotonin and histamine. Also, once triggered inflammation is propagated through the action of integrin-adhesin interactions, endothelial cell factors, and other serum factors. Thus, while EPA may serve as a substrate in AA metabolic pathways, it is presently unclear what compositions might be used topically to prevent or inhibit epithelial inflammation.